Chromogranin A is the quantitatively major soluble protein costored and coreleased with catecholamines from storage vesicles in adrenal medulla, sympathetic nerves, and brain. Its measurement provides a probe of both the extent and the mechanism (exocytotic or otherwise) of catecholamine release. Our past work has included purification and characterization of chromogranin A from catecholamine storage vesicles in several species, development of species-specific chromograin A radioimmunoassays, and studies on the properties, biosynthesis, and release of chromogranin A in several systems. In this proposal, we outline basic studies designed to elucidate further the chemistry (structure), measurement, synthesis, mode of secretion, and regulation of chromogranin A. The proposed studies include: 1) An examination of chromogranin A in large dense cored catecholamine storage vesicles of sympathetic nerve, to ask whether its release mirrors sympathetic as well as adrenal medullary activity; 2) Analysis of chromogranin A synthesis, release, reuptake and function in the model system of cultured chromaffin cells, to investigate its mode of release and its validity as an exocytotic probe; 3) Studies of the genetic control of chromogranin A, using molecular biology and recombinant DNA techniques, to obtain information about its primary structure, its identity in different tissues, and control of its synthesis and secretion; and 4) Elucidation of an adrenal medullary versus a sympathetic neuronal source for plasma chromogranin A. These studies will begin to elucidate chromogranin A's role in sympathoadrenal activity, and will give a firm foundation to emerging clinical studies of chromogranin A in humans.